Risk factors and Outcomes of Dysphagia Among Patients Hospitalized with Acute Intracerebral Hemorrhage: Findings from the Chinese Stroke Center Alliance.

Objective: Dysphagia is a common and severe symptom of acute stroke; however, few studies investigated the prevalence of and risk factors of dysphagia among intracerebral hemorrhage (ICH) patients. We aimed to determine the prevalence and risk factors for dysphagia among acute ICH patients, and assess its impact on outcome of hospitalization. Methods: We collected data of ICH patients from the Chinese Stroke Center Alliance (CSCA) from August 2015 to July 2019 retrospectively. Univariate analysis and multivariable analysis were conducted to identify the factors associated with dysphagia and the outcomes of hospitalization. Results: 32 581 eligible ICH patients were included in the final analysis. According to the results of the swallowing function assessment, patients were divided into 24 084 (73.9%) non-dysphagia group and 8497 (26.1%) dysphagia group. Compared with the non-dysphagia group, the dysphagia group had poor outcomes, including higher incidence of pneumonia (60.2% vs 17.3%, OR 4.82, 95% CI 4.53-5.13) and in-hospital mortality (3.5% vs 0.3%, OR 5.96, 95% CI 4.41-8.06), longer length of stay (P < .01), higher hospitalization cost (P < .01), and higher medicine cost (P < .01). In multivariable analysis, the incidence of dysphagia was independently associated with older age (OR 1.10, 95% CI 1.09-1.11), male sex (OR 1.13, 95% CI 1.06-1.20), arrival at the hospital by emergency medical services (OR 2.11, 95% CI 1.99-2.24), lower Glasgow Coma Scale (GCS) score (per point decrease) (OR 0.78, 95% CI 0.77-0.78), history of ICH (OR 1.25, 95% CI 1.17-1.35), and higher glucose level (OR 1.09, 95% CI 1.07-1.10). Conclusions: More than one-quarter of acute ICH patients were diagnosed with dysphagia, which was associated with poor hospital outcomes. The early identification and management of dysphagia may reduce the possibility of stroke-associated pheumonia, shorten the length of hospital stay, and reduce medical cost.

Clinical effectiveness of Qilong capsule in patients with ischemic stroke: A prospective, multicenter, non-randomized controlled trial.

BACKGROUND: The Qilong capsule (QLC) is a Chinese patented medicine characterized by an equal emphasis on replenishing Qi and activating blood circulation. In 2000, China's FDA approved the use of QLC for ischemic stroke (IS). However, there is not yet much high-quality evidence of the clinical effectiveness of QLC combined with conventional treatment (CT) for IS with Qi deficiency and blood stasis syndrome. PURPOSE: In this study, we conducted a prospective, multicenter, non-randomized controlled trial at 7 hospitals in China to investigate the clinical effectiveness of QLC combined with CT for IS with Qi deficiency and blood stasis syndrome. METHODS: Participants aged 35 to 80 years old diagnosed as IS with Qi deficiency and blood stasis syndrome in TCM were recruited. Participants were treated with QLC (intervention group) or non-QLC (control group). The intervention course of QLC was 12 weeks. All participants in two groups received standard treatment. All participants returned for in-person follow-up visits at the 12th week and 24th week. Primary outcome measures included a modified Rankin Scale (mRS), the National Institute of Health Stroke Scale (NIHSS), and the Barthel Index (BI). Secondary outcome measures included TCM syndromes (Qi deficiency syndrome score, blood stasis syndrome score), psychological index (self-rating depression scale, SDS; self-rating anxiety scale, SAS), blood lipid index, blood coagulation index, homocysteine, and favorable functional outcome (mRS 0 - 3). Multiple imputations were used for any missing data. Propensity score matching (PSM) was used to deal with any confounding factors (age, gender, scale score, etc.). Rank alignment transformation variance analysis (ART ANOVA) and generalized linear mixed model (GLMM) were introduced to improve the scientific and accuracy of repeated measurement data. All statistical calculations were carried out with R 3.6.1 statistical analysis software. RESULTS: A total of 2468 participants were screened from November 2016 to January 2019. Finally, 2302 eligible participants were included in the analysis. There were 1260 participants in the intervention group (QLC group) and 1042 participants in the control group (non-QLC group). After PSM matching, sub-samples of 300 participants in the QLC group and 300 participants in the non-QLC group were finally formed. The final results of clinical effectiveness are the same results shared by the total samples and sub-samples after PSM. In the 24th week after treatment, QLC combined with CT proved to be significantly better than CT alone in reducing the scores of mRS (p < 0.05), NIHSS (p < 0.001), Qi deficiency syndrome (p < 0.01), and blood stasis syndrome (p < 0.001), SAS (p < 0.05), as well as in improving BI score (p < 0.05). The favourable functional outcome (mRS score of 0 to 3 at week 12) was statistically different between QLC and non-QLC group in the sub-samples (p < 0.01, 97% vs 91.7%). The results of the ART ANOVA showed that the improvement of mRS (p < 0.01), BI (p < 0.05) and NIHSS (p < 0.001) in QLC group was better than non-QLC group when the interaction effect was considered. The results of GLMM showed that the reduction of mRS and NIHSS scores of patients in the QLC group were better than those of the non-QLC group (p < 0.001). The BI score of the QLC group in the sub-samples after PSM increased more than the non-QLC group (p < 0.001). There was no evidence showing that QLC can cause serious adverse reactions (ADRs) in treating patients with IS. CONCLUSION: QLC combined with CT was better than CT alone in reducing mRS score, NIHSS score, Qi deficiency syndrome score, blood stasis syndrome score, and SAS score, as well as improving BI score after treatment. Further high-quality RCTs are needed to confirm the positive results. The study protocol was embedded in a registry study that registered in the Clinical Trials USA Registry (registration No. NCT03174535).

Hospital management of major stroke types in Chinese adults: a population-based study of 20 000 hospitalised stroke cases.

OBJECTIVES: To compare hospital treatments for major stroke types in Chinese adults by stroke pathological types, sex, age, calendar year, hospital tier, region and other factors. DESIGN: Cross-sectional analysis of medical records retrieved from 20 229 stroke cases in the China Kadoorie Biobank. SETTING: Ten diverse areas (five urban, five rural) in China. PARTICIPANTS: First-incident stroke cases who were recruited during an 11-year follow-up of 0.5M participants in the China Kadoorie Biobank. METHODS: Electronic copies of medical records of stroke cases were retrieved for clinical adjudication by local neurologists. Stroke cases were classified as ischaemic stroke (IS) (including lacunar infarction (LACI) and non-LACI (non-LACI)), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) and unspecified stroke types. RESULTS: Among 20 299 first-ever stroke cases, 17 306 (85%) had IS, 7123 had non-LACI, 6690 had LACI, 3493 had silent LACI, 2623 (13%) had ICH and 370 (2%) had SAH. Among IS cases, antiplatelet treatment was used by 64% (65% non-LACI, 66% LACI, 56% silent LACI), lipid-lowering by 50% (52% non-LACI, 53% LACI, 43% silent LACI) and blood pressure-lowering by ~42% of all IS types, with positive trends in the use of these treatments by calendar year and hospital tier. Among ICH cases, 53% used blood pressure-lowering and 10% used lipid-lowering treatments, respectively. In contrast, traditional Chinese medicines (TCMs) were used by 59% of IS (50% non-LACI, 62% LACI, 74% silent LACI), 38% of ICH and 30% of SAH cases, with positive trends by calendar year and by hospital tier. CONCLUSIONS: Among IS cases, use of antiplatelet and lipid-lowering medications increased in recent years, but use of TCM still exceeded use of blood pressure-lowering treatment. In contrast, blood pressure-lowering treatment was widely used for ICH, but only half of all ICH cases used blood pressure-lowering treatment.

Association between tea consumption and cognitive impairment in middle-aged and older adults.

BACKGROUND: Biologic studies have suggested that tea may have neuroprotective activity. However, tea's protective effect on cognitive function is controversial in human epidemiological studies, and no data, including the middle-aged, are available. The objective of this study was to investigate the association of habit, frequency, and types of tea consumption with incident cognitive impairment in middle-aged and older adults. METHODS: Data from the Asymptomatic Polyvascular Abnormalities in Community study were used (aged over 40y). We gathered information on tea consumption, including habit, frequency, and types, via a standardized questionnaire and assessed cognitive function by Mini-Mental State Examination (MMSE) and/or Montreal Cognitive Assessment (MoCA). Three thousand eight hundred sixty-eight and 806 participants were selected in MMSE and MoCA subgroups. Multivariate logistic regression models were utilized to examine associations between tea consumption and cognitive impairment in middle-aged and older participants. RESULTS: In MMSE analyses, after adjustment for potential confounding factors, habitual (odds ratio (OR) 0.47, [95% confidence interval (CI) 0.33-0.68], p < 0.001) and high frequency (p trend < 0.001) of tea intake were associated with a lower risk of cognitive impairment. The risk of cognitive impairment was lower in green tea consumption (OR 0.36, [95% CI 0.22-0.61], p < 0.001) than other types (OR 0.59, [95% CI 0.38-0.91], p = 0.017). In MoCA analyses, we got similar results. CONCLUSIONS: Habitual tea consumption, especially high-frequency and green tea consumption, was significantly associated with a lower prevalence of cognitive impairment in middle-aged and older individuals.

Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Danhong injection (DHI) has been widely prescribed to patients with acute ischemic stroke (AIS). However, due to methodological deficiencies, previous research has not yet provided rigorous evidence to support the use of DHI in the treatment of AIS. Therefore, we designed this multicenter, randomized, controlled, and double-blind trial to evaluate the efficacy and safety of DHI for AIS. METHODS/DESIGN: It is a randomized, multicenter, double-blind, placebo-controlled, adaptive clinical trial. A total of 864 eligible patients will be randomized into either the DHI or placebo group in a 2:1 ratio. All patients will be given the standard medical care as recommended by guidelines. Participants will undergo a 2-week treatment regimen and 76-day follow-up period. The primary outcome is the proportion of patients with a favorable outcome, defined as a score of 0-1 on the modified Rankin scale at day 90. Secondary outcomes include a change in the total score of the Chinese medicine symptom scales of "Xueyu Zheng" (blood stasis syndrome), the proportion of patients with a Barthel Index score of ≥90, the proportion of patients with an improvement in NIHSS score of ≥4 or NIHSS score of 0-1, quality of life measured by the EQ-5D scale, etc. Safety outcomes such as global disability (mRS ≥3) at day 90 will also be assessed. The changes in mRNA and microRNA profiles in 96 patients selected from certain centers will also be assessed. As this is an adaptive design, two interim analyses are prospectively planned, which will be carried out after one-third and two-thirds of patients have completed the trial, respectively. Based on the results of the interim analyses, the Data Monitoring Committee (DMC) will decide how to modify the study. DISCUSSION: This trial will provide high-quality evidence for DHI in treatment of AIS. TRIAL REGISTRATION: Clinical Trials.gov NCT01677208 (Date of registration 22 December 2012).

[Efficacy of yindan xinnaotong soft capsule on cerebral infarction reconvalescents of static blood blocking collaterals syndrome: a randomized controlled study].

OBJECTIVE: To evaluate the efficacy and safety of Yindan Xinnaotong Soft Capsule (YXSC) on cerebral infarction (CI) reconvalescents of static blood blocking collaterals syndrome (SBBCS). METHODS: Totally 118 CI reconvalescents of SBBCS were randomly assigned to the test group (treated by YXSC) and the control group [treated by Naoxintong Capsule (NC)], 59 in each group. The therapeutic course for all was 12 weeks. Changes of National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified Rankin Scale (mRS), Chinese medical syndrome scores, and serum lipid indices were observed in the two groups. RESULTS: Compared with the control group, the patient proportion of improving activities of daily life by more than or equal to 75 score was elevated (80.7% vs 62.5%; P < 0.05). Compared with before treatment in the same group, the NIHSS score decreased at post-treatment 4, 8, and 12 weeks in the two groups (P < 0.05). The patient proportion of dropped NIHSS score by more than or equal to 5 score was lowered (80.7% vs 57.14%), and the total effective rate of improving Chinese medical syndromes was superior in the test group after 12-week treatment (89.47% vs 71.43%, all P < 0.05). After 12-week treatment there was no statistical difference in the patient proportion of lowering mRS lower than or equal to 2 or blood lipids between the two groups (P > 0.05). CONCLUSION: YXSC showed certain effect in improving activities of daily life, attenuating the neurological impairment, and elevating the total effective rate of improving Chinese medical syndromes in CI patients in the recovery stage.

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE).

BACKGROUND: Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. METHODS/DESIGN: The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30-80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. DISCUSSION: Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer's disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke.

Age differences in clinical characteristics, health care, and outcomes after ischemic stroke in China.

BACKGROUND AND PURPOSE: Little information is available on the effects of age on health care and outcomes of ischemic stroke (IS) in China. Our aim was to evaluated risk factors, health care, and outcomes among age groups including ≤ 45, 46-65, 66-79, and ≥ 80 years and to find whether the outcome was affected by age and health care. METHODS: CNSR is a nationwide prospective registry for patients admitted with acute stroke and prospectively followed up 12-month outcomes. Demographics, socioeconomics, risk factors, health care, and outcomes were analyzed among age groups, and multivariate regression analysis was used to determine the association of outcome and age and health care. RESULTS: We identified 12,415 acute IS patients for analysis. Of 1179 (9.50%) were aged ≥ 80 years. In terms of risk factors, cardiac diseases were significantly more frequent in patients ≥ 80 years, behavioral risk factors were more common in younger patients, and hypertension, hyperlipidemia, and diabetes were more seen in 46-79 patients. The use of health care varied among groups and was significantly lower in ≥ 80 years especially in secondary prevention. The very old patients had the worst outcomes even after adjusting by prognostic factors; however, adjusting forward by health care, the extent of differences decreased. CONCLUSIONS: In CNSR, differences in stroke clinic characteristics and health care were observed among various age groups, and the old patients, receiving lower levels of stroke care, had the worst outcomes. Knowledge of the age differences in ischemic stroke may be helpful to appropriately allocate the limited health resources and to improve stroke outcomes.

[Post-marketed re-evaluation of fleabane injection and Dengzhan Shengmai capsule study on treatment in patients with ischemic stroke].

OBJECTIVE: To verify the efficacy and safety of post-marketed fleabane injection combined with Dengzhan Shengmai capsules in the treatment of ischemic stroke (IS). METHOD: A multicentre, prospective, practical, randomized controlled study was carried out to compare the efficacy and safety of Dengzhan group (n = 343) and western medicine group (n = 335), appling "clinical study central stochastic system". The treatment of Dengzhan group is using fleabane injection in acute stage and Dengzhan Shengmai capsules in convalescence. The primary indexes of effect evaluation are the important outcome events in 360 days' follow-up, including mortality, recurrence, disability and quality of life to reflect the effect of clinical study. The indexes of safety evaluation involve laboratory examination results and incidence of adverse events. RESULT: After 360 days' follow-up, 4 people died of IS in Dengzhan group, and the mortality rate of which is 1.17%, while 16 died in Western medicine group (WM group), and the mortality rate is 4.78%, suggesting that the mortality rate of Dengzhan group is significantly lower than WM group (P<0.05). Eleven cases recurred in Dengzhan group, and the recurrence rate of which is 3.21%, while 12 recurred in WM group, and the recurrence rate is 3.59%, indicating that the recurrence rate of Dengzhan group is slightly lower than WM group. The disability rate of Dengzhan group is 39.53%, among which the rate of severely disabled cases are 1.49%, while the disability rate of WM group is 40.13%, among which the rate of severely disabled cases are 3.13%, suggesting that the disability rate of Dengzhan group is lower and the severity of disability is also lighter than WM group. In the field of quality of life, the activity ability and the upper limb function store of stroke patients in Dengzhan group improved far much better than WM group (P<0.05). Analysis of safety suggested that, adverse events occurred in 11 cases in Dengzhan group, among which 4 cases is related with the drug treatment, the incidence of adverse events of which is 1.17%, and the main manifestations involve fever and chilling, rash, nausea, dizziness, palpitation, etc. which were all appeared after the treatment of fleabane injection, and disappeared 1 to 2 days after drug withdrawal. 13 cases occurred abnormal liver function and 2 cases abnormal kidney function in Dengzhan group. According to the judgment of clinical physicians, 3 case of ALT abnormality is possibly related to the treatment, the others are all unrelated with the treatment. CONCLUSION: Fleabane injection and Dengzhan Shengmai capsules are all safe and effective TCM in the treatment of ischemic stroke.

[Post-marketing re-evaluation of Kudiezi injection study on early treatment in patients with ischemic stroke].

OBJECTIVE: To study the effect and safety of Kudiezi injection on patients with acute ischemic stroke. METHOD: Seven hundreds patients were divided into two groups by central randomization system. The study group, 346 cases, was treated with kudiezi injection plus traditional Chinese medicine (TCM) synthesis rehabilitation project, and the control group, 354 cases, was treated with synthetic rehabilitation project. The patients were treated for 10 to 21 days. Before treatment and at the 7th, 14th and 21th day of treatment, the indexes include NIHSS used for evaluating the neurological deficit degree and the motor function score (Fugl-Meyer) for evaluating motor function were observed. The safety index is defined by adverse observation event and laboratory test. The incidence of adverse events and laboratory tests results were observed before and after treatment at the same time. RESULT: Application of generalized estimating equation model, we found that as the treatment time, NIHSS score and FMI score of the two groups showed a trend of improvement. And at the 14th days and 21th days of treatment, compared to the control group the treatment group showed significant statistical difference on the impact of NIHSS and FMI (P<0.05). No serious adverse events were observed. CONCLUSION: Kudiezi injection plus TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the neurological deficit and motor function. Kudiezi injection is safe and effective in the treatment of acute ischemic stroke.

Antithrombotic management of ischaemic stroke and transient ischaemic attack in China: a consecutive cross-sectional survey.

1. Little is known about the prevention of secondary stroke in China. In the present study, we assessed the status of antithrombotic management of stroke patients in clinics across China. 2. A cross-sectional survey was conducted in 19 urban neurological clinics. All subjects diagnosed with ischaemic stroke (IS) or transient ischaemic attack (TIA) were enrolled consecutively in the study. Face-to-face interviews were conducted by research assistants using questionnaires on the day of enrollment. The data recorded included demographic and clinical characteristics, medication and reasons for not using medication. Independent predictors for the prescription of antiplatelet drugs were determined using multivariate logistic regression models. 3. Of the 2283 patients with IS or TIA enrolled in the study (34.7% women; mean ( +/- SD) age 65.8 +/- 11.6 years), 1719 (75.3%) had a prescription for antiplatelet therapy. Of the 108 patients with atrial fibrillation, only 14 (13.0%) were receiving warfarin therapy. The main independent factors significantly associated with being on antiplatelet therapy were having basic health insurance (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.09-1.99), government insurance and labour insurance (OR 1.63; 95% CI 1.03-2.59) and a monthly income of > 500 yuan (US$66.70; OR 2.14; 95% CI 1.51-3.03). Being older (OR 0.70; 95% CI 0.50-0.99) and having a severe disability (OR 0.68; 95% CI 0.49-0.97) were associated with lower odds of receiving antiplatelet therapy. 4. Based on the survey results, adherence to guidelines for antithrombotic management in neurological clinics in China is poor. The main reasons contributing to the less than optimal management of stroke patients include negative attitudes among neurologists, a lack of medical insurance, a lower income and being elderly and/or severely disabled.

Management of SAH with traditional Chinese medicine in China.

China lacks large scale authorized epidemiological study results in allusion to subarachnoid hemorrhage (SAH) within recent 15 years since MONICA (multinational monitoring of trends and determinants in cardiovascular disease) study revealed SAH situation in China in 2000. The main cause of SAH in China is aneurysm which takes up 30-50%, while over 90% aneurysm locates at Willis circle. Early surgery for SAH after aneurysm rupture is the dominant procedure to deal with SAH in China. Moreover, calcium antagonists rank the absolute leading position for cerebral vascular spasm (CVS) among medication-based treatment options. However, traditional Chinese medicine such as Salvia miltiorrhiza, Acanthopanax senticosus, Ginkgo biloba, Pueraria lobata, Liguisticum chuanxiong, cow bezoar, Diospyros kaki and Gynostemma pentaphyllum have been proven beneficial in CVS prevention and treatment, while Salvia miltiorrhiza and TCM soup have unique effects on bleeding absorption. In addition, aescine and some TCM soup might relieve strong headache after SAH. In general, TCM integrated with western medicine have shown unique advantages in the current treatment of SAH in China. However, it is a pity that China still lacks larger scale randomized controlled trials and research on SAH treatment focusing on TCM and the related mechanism of TCM on SAH still need to be investigated further.